Association between performance measures and clinical outcomes in patients with heart failure in China: Results from the HERO study

Abstract Background There is great heterogeneity in the quality of care among hospitals in China, but studies on the performance measures and prognosis of patients with heart failure (HF) are still deficient. Hypothesis Performance measures have been used as a guideline to clinicans, however, the association between them and outcomes among HF patients in China remains unclear. Methods We analyzed 4497 patients with HF from the Heart Failure Registry of Patient Outcomes study. Performance measures were determined according to the guidelines, and the patients were divided into four groups based on a composite performance score. Multiple imputation and Cox proportional‐hazard regression models were used to assess the association between the performance measures and clinical outcomes. Results Overall, only 12.5% of patients met the top 25% of the performance measures, whereas 33.5% of patients met the bottom 25% of the measures. A total of 992 (22.2%) patients died within 1 year, involving a larger proportion of patients who had met only the bottom 25% of the performance measures than had met the top 25% (27.0% vs. 16.3%, respectively). The patients who met the top 25% of the measures had a lower 1‐year mortality rate (adjusted hazard ratio: 0.78, 95% confidence interval: 0.61–0.98). Conclusions The association between performance measures and mortality appeared to follow a dose–response pattern with a larger degree of compliance with performance measures being associated with a lower mortality rate in patients with HF. Accordingly, the quality of care for patients with HF in China needs to be further improved.

Heart failure (HF) is the final stage of all cardiovascular diseases.The total number of patients with HF continues to grow owing to population growth and aging, with an estimated 64.3 million affected people worldwide, and the average age of onset has decreased. 1,2HF remains a major clinical and public health problem, with extremely high mortality and readmission rates. 3armacological therapies, including angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs)/ angiotensin receptor blockers and neprilysin inhibitors (ARNIs), betablockers, and mineralocorticoid receptor antagonists (MRAs), have been included in HF management guidelines based on the results of randomized controlled trials. 410] Patients with HF in China have the highest medical burden among those in low-and middle-income countries at RMB 28 974 ($4199). 11,12er the past 20 years, efforts have been made to measure, report, and improve the quality of care for patients with HF to reduce the burden of mortality and readmission.In 2005, the Get With the Guidelines-Heart Failure (GWTG-HF) registry was launched in the United States to improve the quality of care for patients with HF and reduce heterogeneity among hospitals. 13In the past decade, the Chinese healthcare system has also improved the quality of care of patients with HF, and suitable quality measures for the Chinese medical system have been formulated.Although studies have revealed significant differences in performance measures among hospitals, 14,15 current evidence for the relationship between these measures and clinical outcomes is insufficient.To address this issue, we analyzed the association between performance measures and clinical outcomes of patients with HF in China.

| Study population
In the Heart Failure Registry of Patient Outcomes (HERO) study, a prospective, longitudinal, seasonally rotating, multicenter registry study, 5620 patients diagnosed with HF at 73 hospitals in Henan Province from November 2017 to November 2018 were recruited. 7ese hospitals included provincial-, municipal-, and county-level hospitals that cover different geographical areas and with different sizes of referral populations.Baseline data were collected by trained cardiologists to obtain information on patients' sociodemographic characteristics, medical history, diagnosis, and treatment.We excluded patients who were lost to follow-up and those who died in the hospital.

| Performance measures and clinical outcomes
The five performance measures we used were based on the 2020 American College of Cardiology/American Heart Association (AHA) clinical performance and quality measures for adults with HF and the expert consensus on clinical performance and quality measures for adults with HF in China and were as follows 16,17 : (1) the brain natriuretic peptide (BNP)/N-terminal prohormone of BNP (NT-proBNP) test; (2) left ventricular ejection fraction (LVEF) assessment; (3) beta-blocker therapy; (4) ACEI/ARB/ARNI therapy; and (5) MRA therapy.We computed a composite score to reflect the hospital quality of care for HF, calculated as the number of performance measures actually completed by each patient divided by the number of measures that patients should theoretically complete.Based on composite score of performance measures, patients were further divided into quartiles: bottom 25% (N = 1.505), 25%-50% (N = 1320), 50%-75% (N = 1108), and top 25% (N = 564).The 30-day and 1-year mortality and readmission rates of patients with HF were chosen as the clinical outcomes for the present study.Mortality and readmission were defined as death from any cause and hospitalization for HF after discharge, respectively.

| Statistical analysis
Normally distributed continuous variables were presented as means ± standard deviations and compared with one-way analysis of variance, whereas non-normally distributed continuous variables were displayed as medians (Q1, Q3) and compared with the nonparametric Kruskal-Wallis test.Categorical variables were expressed as percentages and compared using the χ 2 test.Kaplan-Meier curves were plotted to analyze the clinical outcomes and compared using the log-rank test.Multivariable Cox proportional-hazards regression was used to evaluate the association between the completion of performance measures and clinical outcomes, and the models were adjusted for potential confounding variables after multiple imputations of missing data.9][20][21] Second, we adjusted for prescriptions for digoxin, diuretics, acetylsalicylic acid, clopidogrel, statins, and nonvitamin K antagonist oral anticoagulants (NOACs) at discharge.All data analyses were performed using IBM SPSS Statistics for Windows version 27.0 (IBM Corp.).

| Baseline characteristics
Among the 5620 patients with HF and an NYHA class III or IV in the HERO study, those who died during hospitalization (n = 98) or were lost to follow-up (n = 1025) were excluded.Hence, 4497 patients were included in this study (Figure 1 1).Patients in the top 25% of the composite score were more likely to be treated at hospitals with more cardiologists (median, 21 vs. 15, p < .001),beds (median, 124 vs. 110, p < .001)and the capacity for cardiac resynchronization therapy (40.4% vs. 24.0%,p < .001) or cardioverter-defibrillator implantation (40.1% vs. 29.2%,p < .001),and more likely to be treated at tertiary hospitals (32.0% vs. 16.6%,p < .001)than those in the bottom 25%.

| Performance measures
The measurements of LVEF and BNP/NT-proBNP were performed in 56.5% and 80.6% of the 4497 patients, respectively (Table 2).Among 656 patients with HFrEF, the usage of ACEI/ARB/ARNI, betablocker, and MRA were 52.5%, 60.5%, and 84.9% respectively, at discharge, which is much lower than in the United States except for MRA therapy. 22

| Clinical outcomes
A total of 992 (22.2%) patients died and 1585 (35.2%) were readmitted for HF after a median follow-up period of 12.9 months (interquartile range: 11.3, 13.1).Figure 2 and Table 3 show the association between performance measures and clinical outcomes.

| DISCUSSION
The main results in this study were as follows.First, for every patient who received high-quality care, more than two received low-quality care.Second, patients admitted to hospitals with more cardiologists and beds or affiliated with medical universities were more likely to receive high-quality care.Third, the 30-day and 1-year mortality rates of patients receiving high-quality care were significantly lower than those of patients receiving low-quality care, although the readmission rates did not differ between them.This association persisted even after adjusting for relevant confounding factors.
Previous studies that have addressed the associations between process performance measures and clinical outcomes have primarily focused on patients with chronic HF and mortality in different   [25][26][27][28] a conclusion that was also confirmed in the China-HF registry study. 29 speculated on the main reasons for the above-mentioned results.First, the degree of compliance with performance measures is related to patient characteristics, such as economic and educational levels: patients with a low income and educational level and more complications (CHD, AF/AFL, DM, hypertension, COPD) meet relatively few of the performance measures included in our composite score.1][32][33] Second, the low number of prescriptions for guideline- recommended medications may also be attributed to the fact that LVEF is not evaluated in some patients, resulting in patients with HFrEF being overlooked.Hence, although a substantial opportunity for improvement in the performance measures themselves remains, more patients should be detected with current measures for patients with HFrEF, and heterogeneity in HF care among hospitals should be reduced.A similar conclusion was made by Gupta et al. 14 In addition, the low utilization rate of ARNIs during the study period can probably be attributed to their relatively recent approval for the market in China (2017): they were not included in the national health insurance catalog until 2020 and the use of ARNIs was greatly impacted by the inexperience of clinicians and the financial situation of the patients.
With the continuous improvement in clinicians' awareness and prescription of these drugs, adherence to performance measures has greatly improved, and the prescription rate of ARNIs increased to 66% by 2020. 34As for MRA therapy for patients with HFrEF, our study showed 84.9% of patients were treated with MRA, showing a large treatment gap compared with 33% of patients treated with MRA in the Change the Management of Patients with Heart Failure registry.This may be due to the fact that the patients included in our study were all NYHA III to IV patients with acute HF, and the proportion of patients with eGFR > 30 mL/min/1.73m 2 and serum potassium < 5.0 mmol/L was relatively high.
6][37] An analysis of the quality of care for other diseases in China, including acute myocardial infarction, cerebral ischemic stroke, chronic obstructive pulmonary disease, and bacterial pneumonia, revealed that most hospitals had low adherence to performance measures, and that hospitals exhibited large heterogeneity in the quality of care. 38Our results may guide hospital policies aimed at organizational changes to reduce gaps in the care of patients with HF.
Most importantly, we have provided new information about the relationship between performance measures and outcomes in patients with HF.Higher adherence to performance measures was related to lower 1-year mortality, even after adjusting for related confounding factors.This was consistent with the Organized  suggested that increased adherence to performance measures was associated with reduced mortality and readmission rates.Specifically, in that study, patients with HF admitted to hospitals that provided specific process-of-care improvements had lower mortality and readmission rates than those who were not (34.8% vs. 38.2%). 39milarly, the Danish Heart Failure Registry (DHFR) demonstrated that meeting process performance measures recommended in clinical guidelines for HF care was associated with a significant reduction in 1-year mortality among patients with HF. 40 However, we observed no statistically significant difference between the readmission rate and the compliance with performance measures, which may be explained by the fact that readmission for HF has more to do with socioeconomic determinants of health and the severity of the patient's condition than with the quality of care provided.
In addition to the performance measures included in our study, the performance and quality measures recommended in the guidelines also include exercise training and patient self-care education.A systematic review showed that patient education for HF significantly influenced the readmission rate. 41However, further analysis of patients with HFrEF in the DHFR study demonstrated that patient education was associated with lower hospital bed daily use but not with readmission risk, while exercise training was associated with both reduced 1-year mortality and readmission. 42However, in our observational study, exercise training and patient education were not provided to the patients.Therefore, the lack of significance in the relationship between the readmission rate and performance measures may also be affected by the lack of implementation of these two measures.In the future, exercise training and education for patients with HF should be increased to reduce mortality and readmission and further improve the quality of life.
The GWTG-HF is a national hospital-based quality improvement program launched by the AHA in 2005 to improve the quality of care provided for HF, which accounts for the large gap in the quality of such care between China and the United States. 13The gap in performance measures for patients with HF among different hospitals has gradually narrowed, and the patient prognosis has greatly improved with the T A B L E 3 Association between performance measures and clinical outcomes after multiple imputations.development of the GWTG-HF, which is unrelated to the volume and academic status of hospitals. 24,43Nearly 20 years of experience with this program and our results provide lessons that may benefit China.The Chinese government could launch a hospital-based medical quality monitoring system, publicly report performance measures, and financially reward or penalize hospitals, as appropriate.This may reduce the gap in the quality of medical care, stimulate the improvement of such care, and improve the prognosis of patients with HF in China.

| LIMITATIONS
This study had several limitations.First, approximately half of the patients did not undergo LVEF assessment, possibly resulting in a portion of patients with HFrEF not being removed from the study.All echocardiograms were obtained in local hospitals, which may in part be the cause of heterogeneity in the LVEF.Currently, an accurate assessment of compliance with the Chinese guidelines is not feasible.Second, although the performance measures recommended in the guidelines also include exercise training and patient education, regrettably, these two measures were not included in this study.Finally, our study had a short follow-up period (1 year) and did not provide further evidence of the relationship between performance measures and long-term prognosis.

| CONCLUSION
In conclusion, the quality of care for HF in China varies greatly among hospitals.Meeting process performance measures that reflect the recommendations of the clinical guidelines for HF care was associated with significantly reduced mortality among patients with HF.
geographical and socioeconomic areas of the world.This study from China aims to add to the current heterogeneity of healthcare for cardiovascular disease, worldwide.The HERO study, which included patients with HF in Henan Province, is one of the largest registered HF-research cohorts in China.The data released from the seventh national census by the National Bureau of Statistics in 2021 confirmed that Henan Province is one of the most populous provinces in China, with a population of almost 100 million, accounting for 7.04% of the total population, and it is usually regarded as representative of the Chinese population. 23Our results demonstrated that the gap in the quality of care for HF remains large, with more than double the number of patients who receive F I G U R E 1 Flowchart.NYHA, New York Heart Association.T A B L E 1 Patient and hospital baseline characteristics.
T A B L E 2 Performance measures at discharge.